Validating a bimodal intravascular ultrasound (IVUS) and near-infrared fluorescence (NIRF) catheter for atherosclerotic plaque detection in rabbits

Abstract

Coronary artery disease is characterized by atherosclerotic plaque formation. Despite impressive advances in intravascular imaging modalities, in vivo molecular plaque characterization remains challenging, and different multimodality imaging systems have been proposed. We validated an engineered bimodal intravascular ultrasound imaging (IVUS) / near-infrared fluorescence (NIRF) imaging catheter in vivo using a balloon injury atherosclerosis rabbit model. Rabbit aortas and right iliac arteries were scanned in vivo after indocyanine green (ICG) injection, and compared to corresponding ex vivo fluorescence and white light images. Areas of ICG accumulation were colocalized with macroscopic atherosclerotic plaque formation. In vivo imaging was performed with the bimodal catheter integrating ICG-induced fluorescence signals into cross-sectional IVUS imaging. In vivo ICG accumulation corresponded to ex vivo fluorescence signal intensity and IVUS identified plaques.

Keywords: (110.7170) Ultrasound; (170.0110) Imaging systems; (170.2150) Endoscopic imaging; (170.6280) Spectroscopy, fluorescence and luminescence.

Fig. 1

Overview of the IVUS-NIRF imaging system with a diagram of the catheter’s tip. PMT stands for photomultiplier tube and is the optical detector in NIRF.

Fig. 2

Ex vivo near-infrared fluorescence (NIRF) images of rabbit aortas. Each column represents a different group, with 3 rabbits per group. Rabbit aortas were cut in two sections to fit in the field of view of the imaging system. For each panel, the upper part represents the aortic arch, the thoracic aorta and the proximal abdominal aorta. The lower part represents the continuation of the abdominal aorta and the left (top) and right (bottom) iliac arteries. Green brackets indicate areas of balloon injury. A.U., arbitrary units.

Fig. 3

Signal comparison for selected arterial segments in ex vivo near-infrared fluorescence (NIRF) images. The distal 0-40 mm abdominal aorta and the right iliac artery are the balloon-injured regions, when performed. The ratios were obtained by dividing the mean right iliac artery (or distal 0-40 mm abdominal aorta) signal by the mean left iliac artery (or distal 40-80 mm abdominal aorta) signal for each animal. The error bars are the standard errors on the mean for the three rabbits of each group.

Fig. 4

Paired ex vivo near-infrared fluorescence (NIRF) and white light images of three longitudinally opened rabbit aortas, one for each group. (a, c, e) Ex vivo fluorescence images of excised aorta and iliac arteries showing increased ICG-accumulation in balloon-injured areas and in rabbits fed a cholesterol-enriched diet. (b, d, f) White light images of excised aorta and iliac arteries showing corresponding macroscopic plaque formation. The red circle shows scar tissue caused by the balloon injury. The green arrows show the regions that underwent balloon injury, including the right iliac artery (bottom).

Fig. 5

Integrated intravascular ultrasound (IVUS) and near-infrared fluorescence (NIRF) imaging in vivo. (a-e) Integrated IVUS/NIRF images of aortic segments of rabbits fed a cholesterol-enriched diet; (f) image of a rabbit on a regular diet, outside balloon-dilated area. The contour in the IVUS image represents the fluorescence signal intensity. Red arrows show increased echogenicity in (a, e) and intimal thickening in (b, f). Scale bar is 1 mm. A.U., arbitrary units.

Fig. 6

Comparison of in vivo and ex vivo near-infrared fluorescence (NIRF) images and corresponding white light images of rabbit aortas. (a, e) In vivo fluorescence imaging; (b, f) corresponding ex vivo fluorescence imaging; (c, g) white light images of longitudinally opened abdominal aorta and iliac arteries of 2 balloon-injured rabbits. The green arrows show the regions that underwent balloon injury, including the right iliac artery (bottom). The red arrows show corresponding enhanced ICG-accumulation visible in both in vivo and ex vivo fluorescence imaging. (d, h) Integrated intravascular ultrasound (IVUS)/NIRF cross-sectional images at the locations indicated by the red arrows.

Fig. 7

Effect of blood attenuation compensation on in vivo fluorescence images. (a, d, g) In vivo fluorescence images of the abdominal aortas of 3 rabbits without blood attenuation compensation; (b, e, h) Corresponding in vivo fluorescence images after blood attenuation compensation; (c, f) Corresponding ex vivo fluorescence images; (g, h) Integrated intravascular ultrasound (IVUS)/near-infrared fluorescence (NIRF) cross-sectional images (g) without and (h) with blood attenuation compensation.